DESCRIPTION: Substantial evidence indicates that genetic differences among individuals have a major effect on risk of chronic periodontitis. It is very likely this disease has a complex etiology, however, with inherited variation at multiple genes interacting with environmental factors such as smoking, hygiene, exposure to pathogens to determine individuals' disease risk. Our studies of adult twins demonstrated heritability of 50% and higher for quantitative measures such as mean attachment loss (AL) and percentage of sites with AL greater than thresholds of 2 mm, 3 mm or 4 mm. Our gene mapping analyses of early onset aggressive periodontitis families have identified dozens of candidate genes with strong to moderate support for involvement in this disease subtype. We have also recently shown that periodontitis-related phenotypes such as serum immunoglobulin levels have highly significant heritability. Major advances in human molecular genomics techniques for analysis of single nucleotide polymorphisms (SNPs) and statistical genetic strategies such as haplotype mapping may provide greatly increased power to identify genes underlying complex traits such as periodontitis. A critical component needed for success in this approach is availability of very large, high quality clinical populations. We propose to apply these tools and approaches to advance understanding of the genetic and environmental basis of susceptibility to chronic periodontitis by testing over 500 SNPs in over 100 candidate genes for association with periodontitis in i.) 7,300 subjects from the NHANES III study for whom DNA is available; ii.) 200 adult subjects with severe chronic periodontitis and 100 healthy controls recruited in Minnesota; and iii.) in 234 subjects from our previously reported twin study that demonstrated high heritability of chronic periodontitis; iv) by evaluating alternative quantitative and disease classification (discrete) measures in these clinical populations; and v.) by analyzing environmental risk factors in all samples and antibody responses to periodontal pathogens in the NHANES sample. [unreadable] [unreadable]